1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 13781250, compound

HRID 1626743Notes

Reaction equation

HRID 1626743 reaction equation
N12CCCN=[C:7]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2.[C:12]12([C:22](=[O:25])[CH:23]=[CH2:24])[CH2:21][CH:16]3[CH2:17][CH:18]([CH2:20][CH:14]([CH2:15]3)[CH2:13]1)[CH2:19]2.[Cl-].[O:27]=C(C)C[N+]1C=CC=CC=1>C(O)C>[C:12]12([C:7]3[CH:6]=[C:5]([OH:27])[CH:4]=[CH:3][CH:2]=3)[CH2:21][CH:16]3[CH2:15][CH:14]([CH2:20][CH:18]([CH2:17]3)[CH2:19]1)[CH2:13]2.[C:12]12([C:22](=[O:25])[CH:23]=[CH2:24])[CH2:19][CH:18]3[CH2:17][CH:16]([CH2:15][CH:14]([CH2:20]3)[CH2:13]1)[CH2:21]2

Participants

6

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27341211-Acetonylpyridinium ChlorideHCID 13781250HCID 13781250, compound

Product 2

HCID 13781250HCID 13781250, compoundHCID 66680555HCID 66680555, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A THF solution (20.0 mL, 10.0 mmol) comprising 1 mol/L of vinylmagnesium bromide was slowly added dropwise to a THF (45 mL) solution comprising 2.23 g (5.00 mmol) of N-methoxy-N-methyladamantan-1-carboxamide that had been cooled in a bath containing ice and salt while keeping the THF solution at −10 to 0° C. Thereafter, the mixture was stirred at 0° C. for 1 hour, and stirred at room temperature overnight. The reaction mixture was slowly added dropwise, using a Pasteur pipette, to saturated ammonium chloride water that had been cooled in a bath containing ice and salt, while keeping it at −10 to −5° C. After the completion of the dropwise addition, the mixture was heated to 0° C. Since the mixture comprises two layers, the water layer was separated, and ethyl acetate extraction was performed three times. Subsequently, the primarily separated organic layer and the combined ethyl acetate layers were combined, and the organic layer was washed with saturated ammonium chloride water 5 times, and with brine once. Drying over sodium sulfate, filtration, condensation, and drying under reduced pressure at room temperature for 3 hours were performed, thereby giving the crude product of 1-(adamantan-1-yl)prop-2-en-1-on (containing 1.56 g of impurities such as 3-[methoxy(methyl)amino]-1-(adamantan-1-yl)propan-1-on, etc.) The crude product was used in the next reaction without purification. Under an Ar atmosphere, 1.43 g of 1,8-diazabicyclo[5.4.0]undeca-7-en (DBU) was added to an ice-cooled suspension comprising 1.18 g of the crude product of 1-(adamantan-1-yl)prop-2-en-1-on, 1.60 g of 1-(2-oxopropyl)pyridinium chloride, 1.18 g of molecular sieves 4A, and ethanol (24 mL), and the mixture was stirred at room temperature for 2 days. Under ice-cooling, 1N HClaq. was added to the reaction mixture, the pH was adjusted to 1, and ethyl acetate extraction was performed. The organic layer was separated, and washed with brine three times, followed by drying over sodium sulfate, filtration, condensation, and drying under reduced pressure at room temperature for 1 hour, thereby giving the crude product (936 mg) of 3-(adamantan-1-yl)phenol. This crude product and the crude product of 3-(adamantan-1-yl)phenol (456 mg) obtained from the crude product of 400 mg of 1-(adamantan-1-yl)propa-2-en-1-on under the same conditions were combined. Then this crude product was separated and purified by silica gel column chromatography, thereby giving 222 mg of 3-(adamantan-1-yl)phenol (yield: 9.7%).

Workup

  1. customwas used in the next reaction without purification
  2. temperaturecooled suspension
  3. temperatureUnder ice-cooling
  4. additionwas added to the reaction mixture
  5. extractionthe pH was adjusted to 1, and ethyl acetate extraction
  6. customThe organic layer was separated
  7. washwashed with brine three times
  8. dry with materialby drying over sodium sulfate, filtration, condensation
  9. customdrying under reduced pressure at room temperature for 1 hour
  10. customgiving the crude product (936 mg) of 3-(adamantan-1-yl)phenol

Sources & evidence

ORD record
ord-1a6fce1ca3414bfabe6b1d652df08742
Source dataset
uspto-grants-2014_07
Patent number
US08785473B2

Reaction notes

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